Two-Locus Likelihoods under Variable Population Size and Fine-Scale Recombination Rate Estimation

Two-locus sampling probabilities have played a central role in devising an efficient composite likelihood method for estimating fine-scale recombination rates. Due to mathematical and computational challenges, these sampling probabilities are typically computed under the unrealistic assumption of a constant population size, and simulation studies have shown that resulting recombination rate estimates can be severely biased in certain cases of historical population size changes. To alleviate this problem, we develop here new methods to compute the sampling probability for variable population size functions that are piecewise constant. Our main theoretical result, implemented in a new software package called LDpop, is a novel formula for the sampling probability that can be evaluated by numerically exponentiating a large but sparse matrix. This formula can handle moderate sample sizes ($n \leq 50$) and demographic size histories with a large number of epochs ($\mathcal{D} \geq 64$). In addition, LDpop implements an approximate formula for the sampling probability that is reasonably accurate and scales to hundreds in sample size ($n \geq 256$). Finally, LDpop includes an importance sampler for the posterior distribution of two-locus genealogies, based on a new result for the optimal proposal distribution in the variable-size setting. Using our methods, we study how a sharp population bottleneck followed by rapid growth affects the correlation between partially linked sites. Then, through an extensive simulation study, we show that accounting for population size changes under such a demographic model leads to substantial improvements in fine-scale recombination rate estimation. LDpop is freely available for download at https://github.com/popgenmethods/ldpopComment: 32 pages, 13 figure

Comparison of speech intelligibility in cockpit noise using SPH-4 flight helmet with and without active noise reduction

Active Noise Reduction (ANR) is a new technology which can reduce the level of aircraft cockpit noise that reaches the pilot's ear while simultaneously improving the signal to noise ratio for voice communications and other information bearing sound signals in the cockpit. A miniature, ear-cup mounted ANR system was tested to determine whether speech intelligibility is better for helicopter pilots using ANR compared to a control condition of ANR turned off. Two signal to noise ratios (S/N), representative of actual cockpit conditions, were used for the ratio of the speech to cockpit noise sound pressure levels. Speech intelligibility was significantly better with ANR compared to no ANR for both S/N conditions. Variability of speech intelligibility among pilots was also significantly less with ANR. When the stock helmet was used with ANR turned off, the average PB Word speech intelligibility score was below the Normally Acceptable level. In comparison, it was above that level with ANR on in both S/N levels

A Likelihood-Free Inference Framework for Population Genetic Data using Exchangeable Neural Networks

An explosion of high-throughput DNA sequencing in the past decade has led to a surge of interest in population-scale inference with whole-genome data. Recent work in population genetics has centered on designing inference methods for relatively simple model classes, and few scalable general-purpose inference techniques exist for more realistic, complex models. To achieve this, two inferential challenges need to be addressed: (1) population data are exchangeable, calling for methods that efficiently exploit the symmetries of the data, and (2) computing likelihoods is intractable as it requires integrating over a set of correlated, extremely high-dimensional latent variables. These challenges are traditionally tackled by likelihood-free methods that use scientific simulators to generate datasets and reduce them to hand-designed, permutation-invariant summary statistics, often leading to inaccurate inference. In this work, we develop an exchangeable neural network that performs summary statistic-free, likelihood-free inference. Our framework can be applied in a black-box fashion across a variety of simulation-based tasks, both within and outside biology. We demonstrate the power of our approach on the recombination hotspot testing problem, outperforming the state-of-the-art.Comment: 9 pages, 8 figure

Ethics after theory

Today, architectural theory has atrophied. Despite a perceived need for different theoretical ways of clarifying, explaining and understanding the complex phenomena of contemporary architectural production prior to a designer’s intervention, there are few existing theoretical frameworks. Without either the descriptive or projective enablement by theory, conscientious and critical practices in architecture will have few alternatives against the tide of neoliberal city-making. In this paper, I make a pun of Speaks’s (2006) paper titled, ‘Intelligence after theory’ by arguing that while (design) intelligence is necessary, it is however not sufficient. Ethics is also needed in architecture. Through a brief restatement of a canonical debate in the critical school of architectural theory, I argue why ethics is needed in architecture, and how ethics could be further developed through theory and theorization

Ethics After Theory

Today, architectural theory has atrophied. Despite a perceived need for different theoretical ways of clarifying, explaining and understanding the complex phenomena of contemporary architectural production prior to a designer's intervention, there are few existing theoretical frameworks. Without either the descriptive or projective enablement by theory, conscientious and critical practices in architecture will have few alternatives against the tide of neoliberal city-making. In this paper, I make a pun of Speaks's (2006) paper titled, ‘Intelligence after theory' by arguing that while (design) intelligence is necessary, it is however not sufficient. Ethics is also needed in architecture. Through a brief restatement of a canonical debate in the critical school of architectural theory, I argue why ethics is needed in architecture, and how ethics could be further developed through theory and theorization

From afterthought to precondition: re-engaging design ethics from technology, sustainability, and responsibility

Proceedings of DRS 2016, Design Research Society 50th Anniversary Conference. Brighton, UK, 27–30 June 201

Skin thickness of the anterior, anteromedial, and anterolateral thigh: a cadaveric study for split-skin graft donor sites

Background: The depth of graft harvest and the residual dermis available for reepithelization primarily influence the healing of split-skin graft donor sites. When the thigh region is chosen, the authors hypothesize based on thickness measurements that the anterolateral region is the optimal donor site. Methods: Full-thickness skin specimens were sampled from the anteromedial, anterior, and anterolateral regions of human cadavers. Skin specimens were cut perpendicularly with a custom-made precision apparatus to avoid the overestimation of thickness measurements. The combined epidermal and dermal thicknesses (overall skin thickness) were measured using a digital calliper. The specimens were histologically stained to visualize their basement membrane, and microscopy images were captured. Since the epidermal thickness varies across the specimen, a stereological method was used to eliminate observer bias. Results: Epidermal thickness represented 2.5% to 9.9% of the overall skin thickness. There was a significant difference in epidermal thickness from one region to another (P<0.05). The anterolateral thigh region had the most consistent and highest mean epidermal thickness (60±3.2 µm). We observed that overall skin thickness increased laterally from the anteromedial region to the anterior and anterolateral regions of the thigh. The overall skin thickness measured 1,032±435 µm in the anteromedial region compared to 1,220±257 µm in the anterolateral region. Conclusions: Based on skin thickness measurements, the anterolateral thigh had the thickest epidermal and dermal layers. We suggest that the anterolateral thigh region is the optimal donor site for split-skin graft harvests from the thigh